The Civilization series has consumed more hours of my life than I care to admit. I'm also fond of going back to Age of Mythology and the old Sierra game Pharaoh every few years.
I don't normally replay story focussed games, I think the only one I've completed twice is Final Fantasy 7.
5 is the only one I play these days, I remember really enjoying 4 as well though. Never got round to trying 6.
My first Civ was the original on floppy disk when I was a kid and had absolutely no idea what I was doing. iirc it had an anti piracy feature where every so often it would ask you a question from the manual but I didn't have the manual so I was shit out of luck. Sometimes I'd make it to one of the little cutscenes where the palace gets bigger and I'd be buzzing, that was really all I played for.